This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $185,831 to the University of Pittsburgh for a 2-year research project focused on discovering and developing allosteric inhibitors of the Src-family kinases HCK and FGR as potential treatments for acute myeloid leukemia (AML). The research aims to: 1) Synthesize and test analogs of existing allosteric modulators for the AML-associated kinase HCK, and 2) Identify additional scaffolds for...
This federal Project Grant award from the National Cancer Institute (CFDA 93.398 Cancer Research Manpower) in the amount of $121,857 aims to systematically investigate how anti-cancer drugs modulate T cells in the tumor microenvironment. The key objectives are to: Conduct in silico screening to identify anti-cancer drugs impacting T cell effector function, activation, stemness, and proliferation (Aim I). Perform single-cell CRISPR knockout screening to determine anti-cancer drug targets...
This $385,700 Project Grant award from the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training Program (CFDA 93.859) will fund research at the University of Pittsburgh over a 5-year period from September 2024 to August 2029. The research aims to develop advanced computational and machine learning models that integrate diverse biomedical data, from genetics to transcriptomics and proteomics, to better predict the effects of therapies on diseased cells....
The National Institute of General Medical Sciences (NIGMS) awarded a $752,456 Project Grant under the Biomedical Research and Research Training program (CFDA 93.859) to the University of Pittsburgh. The grant, effective September 1, 2024 through July 31, 2029, supports the development and application of innovative, user-friendly computational technologies for identifying new bioactive small molecules and improving their pharmacological properties. Key focus areas include creating a database of...
This federal Project Grant award from the National Cancer Institute (CFDA 93.396 Cancer Biology Research) provides $391,531 to Yale University to develop technology for directing phosphorylation of specific protein kinase substrates. The goal is to engineer a kinase mutant that can selectively phosphorylate a designer allele of one of its substrates, using knowledge of kinase phosphorylation site specificity. The researchers will establish the feasibility of this approach using the tumor...
The National Cancer Institute (NCI), under the Cancer Research Manpower (CFDA 93.398) federal grant program, awarded a $352,712 Project Grant to The Research Foundation for the State University of New York (Stony Brook University) to define selectivity profiles of clinically approved kinase inhibitors (KIs) against clinically observed MET mutants and calculate optimal KI combinations to maximize selectivity and reduce resistance. The goal is to provide an actionable roadmap for MET...
This Project Grant award of $275,956 from the National Science Foundation's (NSF) Computer and Information Science and Engineering (CISE) program aims to develop an engineered cyber-physical system that combines advanced biological models with artificial intelligence methods for predictive, automated screening of anti-cancer drugs and optimization of their dosing. The key products and services to be delivered under this award include: 1) Adoption of 3D bioprinting to generate vascularized ductal...
This Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) provides $371,427 to Carnegie Mellon University to develop novel high-throughput machine learning approaches for analyzing cell population-wide differences in subcellular object morphology, conformations, and organization using cryo-electron tomography (cryo-ET) data. The key products and services to be delivered include: Domain...
This $2,372,456 Project Grant awarded by the National Cancer Institute (CFDA 93.393 - Cancer Cause and Prevention Research) will support a collaborative research program led by Memorial Sloan Kettering Cancer Center focused on leveraging observational (real-world) data to advance precision oncology. The key products and services to be delivered include: Overcoming methodological barriers in the analysis of observational clinico-genomic data (Project 1) Addressing the role of genetic ancestry...
This Project Grant award of $388,621 from the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training Program (CFDA 93.859) will support the development of novel molecular designs with therapeutic potential. The key objectives are: Developing ligand-heterocycle conjugates as targeted RNA degraders with rapid kinetics and selectivity for cancer-associated G-quadruplexes. Engineering nucleic acid polymers with (thio)phosphoramidate backbones as biostable...
This Project Grant award from the National Cancer Institute (CFDA 93.398 Cancer Research Manpower) provides $147,486 to Carnegie Mellon University to develop novel computational methods for predicting kinase inhibitor off-target activity and optimizing multi-target binding during early-stage drug discovery. The key products and services to be delivered include:
Novel methods to reduce the computational expense of alchemical relative binding free energy (RBFE) simulations while maintaining accuracy, enabling their use for predicting off-target kinase binding.
Integration of these efficient RBFE methods with a multi-objective active learning workflow to optimize ligand binding affinity and selectivity against both a primary kinase target and known off-target kinases. This will be demonstrated for inhibitors of activin-like receptor kinase 2 and a hit compound related to the multi-kinase inhibitor entrectinib.
Establishing the feasibility of free energy-based multi-objective optimization to enhance the efficiency of the early drug development pipeline for targeted cancer therapeutics. The award period runs from Sep 2025 to May 2028.